In diseases with manifestations due to aberrant gene function or deficient function, genes may be regulated through the direct delivery of biologically active molecules, such as nucleic acids, peptides and proteins, to their intracellular and intranuclear sites of action to influence gene expression either directly or indirectly through interference with transcription, translation or transcription factor production and action and also missing or defective protein products may be replaced to provide these types of molecules in individuals with germ-line or somatic mutations. The direct replacement of biologically important proteins in genetically deficient individuals is hampered by both (i) the inability of these proteins to reach intracellular sites and tissue sites such as the central nervous system (CNS) where they normally function and (ii) by the immunogenicity of these proteins.